Ketamine is a dissociative anaesthetic drug which acts on the central nervous system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor. Recently, ketamine has attracted attention as a rapid-acting anti-depressant but other studies have also reported its efficacy in reducing problematic alcohol and drug use. This review explores the preclinical and clinical research into ketamine's ability to treat addiction. Despite methodological limitations and the relative infancy of the field, results thus far are promising. Ketamine has been shown to effectively prolong abstinence from alcohol and heroin in detoxified alcoholics and heroin dependent individuals, respectively. Moreover, ketamine reduced craving for and self-administration of cocaine in non-treatment seeking cocaine users. However, further randomised controlled trials are urgently needed to confirm ketamine's efficacy. Possible mechanisms by which ketamine may work within addiction include: enhancement of neuroplasticity and neurogenesis, disruption of relevant functional neural networks, treating depressive symptoms, blocking reconsolidation of drug-related memories, provoking mystical experiences and enhancing psychological therapy efficacy. Identifying the mechanisms by which ketamine exerts its therapeutic effects in addiction, from the many possible candidates, is crucial for advancing this treatment and may have broader implications understanding other psychedelic therapies. In conclusion, ketamine shows great promise as a treatment for various addictions, but well-controlled research is urgently needed. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
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http://dx.doi.org/10.1016/j.neuropharm.2018.01.017 | DOI Listing |
Nervenarzt
January 2025
Abteilung für Molekulares Neuroimaging, Zentralinstitut für Seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg, 68159, Mannheim, Deutschland.
Background: Novel antidepressive substances are challenging the explanations for the mechanisms of action of traditional psychopharmacology.
Objective: What could be the shared effects of various antidepressants and in this context what role do extrapharmacological factors, such as the body and environment, play?
Material And Method: The available literature on clinical and preclinical data for assumed combined active factors of serotonergic psychedelic drugs, (es)ketamine, monoaminergic antidepressants and zuranolone are presented and the influence of context factors on the individual mechanisms of action is discussed.
Results: There are many indications that classical and novel pharmacological approaches could share similar mechanisms of action in the treatment of depression.
Curr Neuropharmacol
January 2025
Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Depression is a prevalent mental disorder, affecting approximately 300 million people worldwide. Despite decades of research into the underlying mechanisms of depression, a consensus remains elusive. Recent studies have implicated changes in oligodendrocytes and myelin in the pathogenesis of depression.
View Article and Find Full Text PDFAm J Psychiatry
January 2025
Biobehavioral Imaging and Molecular Neuropsychopharmacology Section, NIDA, Baltimore (Levinstein, Budinich, Michaelides); Department of Pathology and Experimental Therapeutics, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona (Bonaventura); Neuropharmacology and Pain Group, Neuroscience Program, IDIBELL-Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona (Bonaventura); Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford (Schatzberg); Experimental Therapeutics and Pathophysiology Branch, NIMH, Bethesda (Zarate); Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore (Michaelides).
Ketamine is a racemic compound and medication comprised of ()-ketamine and ()-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders such as anxiety, obsessive-compulsive, and opioid use disorders.
View Article and Find Full Text PDFMol Psychiatry
January 2025
Siena Brain Investigation and Neuromodulation Lab, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Ketamine, a dissociative compound, shows promise in treating mood disorders, including treatment-resistant depression (TRD) and bipolar disorder (BD). Despite its therapeutic potential, the neurophysiological mechanisms underlying ketamine's effects are not fully understood. This study explored acute neurophysiological changes induced by subanesthetic doses of ketamine in BD patients with depression using electroencephalography (EEG) biomarkers.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Histology and Embryology, Ankara University School of Medicine, Ankara, Turkey.
NMDAR antagonists, such as memantine and ketamine, have shown efficacy in treating neurodegenerative diseases and major depression. The mechanism by which these drugs correct the aforementioned diseases is still unknown. Our study reveals that these antagonists significantly enhance 20S proteasome activity, crucial for degrading intrinsically disordered, oxidatively damaged, or misfolded proteins, factors pivotal in neurodegenerative diseases like Alzheimer's and Parkinson's.
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